Glaser-Hay hetero-coupling in a bimetallic regime: A Ni(II)/Ag(i) assisted base, ligand and additive free route to selective unsymmetrical 1,3-diynes

Article abstract of DOI:10.1039/c7cc05605b

A Ni(OAc)₂/Ag(OTf) catalysed coupling of aryl alkynes and propargylic alcohol/ether/ester gave the corresponding unsymmetrical 1,3-diynes in good to excellent yields. The reaction does not require bases, ligands or additives and shows excellent hetero-selectivity, thereby addressing the current challenges in the field of coupling of two different terminal alkynes.

Full text of DOI:10.1039/c7cc05605b

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Glaser–Hay hetero-coupling in a bimetallic
regime: a Ni(II)/Ag(I) assisted base, ligand and
additive free route to selective unsymmetrical
1,3-diynes†
Cite this:DOI: 10.1039/c7cc05605b
Received 20th July 2017,
Accepted 7th September 2017
Anuradha Mohanty
and Sujit Roy
*
DOI: 10.1039/c7cc05605b
rsc.li/chemcomm
A Ni(OAc)2/Ag(OTf) catalysed coupling of aryl alkynes and propargylic
alcohol/ether/ester gave the corresponding unsymmetrical 1,3-diynes
in good to excellent yields. The reaction does not require bases, ligands
or additives and shows excellent hetero-selectivity, thereby addressing
the current challenges in the field of coupling of two different terminal
alkynes.
The synthesis of unsymmetrical 1,3-diynes has attracted a great
deal of attention due to their widespread applications in
organic synthesis and materials science.1 Due to their ubiquitous
structural motifs, they exhibit a range of biological activities like
antifungal, anticancer, anti-HIV and antibacterial properties, and
also play an important role in the design of functional materials
such as optical materials, conductive plastics, high density
fibres and liquid crystals.2,3 Furthermore, conjugated diynes
have unique behaviour towards transition metals, and these
organometallic materials display various novel properties, such
as luminescence, conductivity, and photovoltaic behavior.4
Therefore, the development of an efficient procedure for the
synthesis of unsymmetrical 1,3-diynes still evokes curiosity and
challenge to a synthetic chemist. Over the past few decades,
Glaser5 and Cadiot–Chodkiewicz6 couplings have been the
major methods for the synthesis of 1,3-diynes. In 1986, Glaser
pioneered the synthesis of poly-yne core structures via the
homo-coupling of terminal alkynes by utilizing the oxidative
Scheme 1 Alkynes to diynes: the journey so far.
dimerization of copper(I)phenylacetylide upon exposure to air.5 leading to decreased reaction times and improved yields of the
During the last few years, various modifications of Cu-salt homo-coupling product.10 Unfortunately, one major drawback
mediated Glaser coupling have been developed (Scheme 1).7–9 of this reaction is chemo-selectivity, which results in a mixture
Among these, special mention may be made of the work by of products when different terminal alkynes are used in situ.
Leigh and co-workers who utilized the bimetallic combination The selectivity towards unsymmetrical 1,3-diynes is improved
of Ni(II) and Cu(I) in stoichiometric quantities to promote the in the Cadiot–Chodkiewicz coupling wherein a terminal alkyne
homocoupling of alkynes in rotaxane synthesis.8c In the Glaser– is reacted with an alkynyl halide in the presence of a Cu salt and
Hay variant, catalytic copper(I) chloride is used in the presence an amine base.6 The use of a halide as a reactant, an amine as a
of stoichiometric tetramethylenediamine (TMEDA) and oxygen, solvent and hydroxylamine hydrochloride as a reductive reagent
brings in complexity to the system in terms of the green demand
and work-up protocol. A bimetallic variant of the above reaction
School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Argul,
has been recently reported.11 A very recent report by Liu et al.
Khurda 752050, Odisha, India. E-mail: sroy@iitbbs.ac.in
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c7cc05605b
describing gold catalysed coupling between an alkyne and an
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Table 1 Optimization of reaction conditionsa
alkynyl hypervalent iodine(III) reagent is also noteworthy.12 In
spite of the success as above, the direct hetero-coupling of two
terminal alkynes leading to selective formation of unsymmetrical
1,3-diynes remains a challenge. In this regard three reports are
noteworthy. Shi and co-workers obtained excellent hetero-
selectivity by using [(dppm)(AuBr)2]/phen as a catalyst and
PhI(OAC)2 (2 equiv.) as an oxidant.13 Yin et al. achieved hetero-
selectivity using Cu(0)/TMEDA as the catalyst and CHCl3/O2 as the
oxidant.14 Lei and co-workers utilized the catalytic combination of
Ni(II)/Cu(I)/TMEDA to achieve hetero-selectivity in which one of the
alkynes is used in 5-fold excess.15 One may note that there exist rich
opportunities in the area of bimetallic/dual-reagent catalysis with
emphasis on green/sustainable chemistry.16 While addressing the
issue of the activation of alkyne and propargyl alcohol, we were
drawn in to the challenge of executing a Glaser–Hay hetero-coupling
for the synthesis of unsymmetrical 1,3-diynes under base, ligand,
additive free conditions. In this communication we are delighted to
report the coupling between an aromatic alkyne and propargylic
substrate using a catalytic combination of Ni(II)/Ag(I) under aerobic
conditions to give rise to the corresponding unsymmetrical
1,3-diyne. The excellent hetero-selectivity and the absence of
any additives in the reaction medium are the most noteworthy
feature of this reaction (Scheme 1).
#
Silver catalyst Nickel catalyst Solvent
3b (%) 4b (%)
1
2
3
4
5
6
7
8
9
AgOTF
AgOTF
AgOTF
AgOTF
AgClO4
AgNO3
Ag2O
Ni(OAc)2Á4H2O 1,4-Dioxane
Ni(OAc)2Á4H2O Toluene
Ni(OAc)2Á4H2O MeCN
Ni(OAc)2Á4H2O DMF
Ni(OAc)2Á4H2O DMF
Ni(OAc)2Á4H2O DMF
Ni(OAc)2Á4H2O DMF
Ni(OAc)2Á4H2O DMF
Ni(OAc)2Á4H2O DMF
Ni(OAc)2Á4H2O DMF
0
0
5
0
9
11
8
8
12
6
8
11
65
20
25
20
0
17
87
56
79
69
64
54
81
0
AgBF4
AgPF6
10 AgSbF6
11 AgOTF
12 AgOTF
13 AgOTF
14 AgOTF
—
DMF
DMF
DMF
DMF
NiCl2
0
NiCl2Á6H2O
Trace
0
0
Ni(PPh3)2Cl2
15
16
17
—
—
—
Ni(OAc)2Á4H2O DMF
c
c
NiCl2Á6H2O DMF
0
25
35
10
15
Ni(OAc)2Á4H2O DMF
Trace
Trace
0
18 AgOTF
19 AgOTF
Ni(PPh3)2Cl2
NiCl2Á6H2O
CH3COOH
CH3COOH
a
Reaction conditions: phenylacetylene 1 (0.25 mmol), propargyl alcohol
2 (0.5 mmol), [Ag] (10 mol%), [Ni] (10 mol%), solvent (1 ml), 110 1C, air,
In a model study, we first examined the cross coupling
between phenyl acetylene 1 and propargyl alcohol 2 in the
presence of catalytic nickel(II) and silver(I) salts but in the
absence of bases and additives in different solvents at 110 1C
b
c
3 h. Yields of isolated pure products. CuI (10 mol%).
under aerobic conditions (Table 1). To our gratification, we elongation in the carbon chain length as in but-3-yn-1-ol
found that with the combination of Ni(OAc)2Á4H2O and AgOTf (Table 2, products 3d, 3h, 3l). The generality of the reaction
the hetero cross coupling reaction dominated over the homo with respect to substitution in the aromatic ring of arylalkynes
coupling and the desired product 3 was obtained in excellent has been tested. Both electron donating as well as electron
yield (Table 1, entry 4). Dimethylformamide happened to be the withdrawing groups are well tolerated (Table 2, products 3e–3s).
solvent of choice (Table 1, entries 1–4). We also tested the Notably in the case of the nitro group, the hetero coupling is
reaction with Ag(I) salts having a bulkier and/or better leaving more facile and the yields of the desired 1,3-diynes have been
anionic counterpart (Table 1, entries 4–10). While in all cases 3 excellent (Table 2, products 3q–3s). The reaction was also tested
were obtained in varying amounts, the yield was highest with with pyridylalkyne as a representative heteroarylalkyne and the
silver triflate (Table 1, entry 4). Note that individually AgOTf or coupling proved to be successful and the corresponding products 3t
Ni(OAc)2Á4H2O could not promote the hetero-coupling reaction and 3p were obtained in 60% isolated yields (Table 2). The
(Table 1, entries 11 and 15). Interestingly, individually AgOTF compatibility of the reaction with propargylic ether and propargylic
was efficient for homo coupling of aryl alkynes (Table 1, entry ester was also established (Table 2, products 3u and 3v). The yield
11), while Ni(OAc)2Á4H2O was inactive suggesting the impor- of the homocoupling products 4 from aryl terminal alkynes varied
tance of the bimetallic combination. It is surprising that other in the range of 3–20% (ESI,† Table TS1).
nickel salts tested also failed to promote the desired coupling
The following experiments provide insights into the initial
reaction (Table 1, entries 13–15). Note that the bimetallic bond activation steps. While silver triflate alone can mediate
combination of Cu(I)/Ni(II) was also ineffective towards hetero- the homocoupling of phenylacetylene, the hetero-coupling with
coupling in the present Glaser–Hay coupling (Table 1, entries 16 propargylic alcohol requires the presence of a Ni(II) catalyst,
and 17). A reaction attempted in an acetic acid medium in the which clearly establishes the bimetallic reactivity. Preliminary
presence of other nickel salts/complexes gave only the homo- investigation on the interaction of Ni(II) and Ag(I) with the
coupling product from phenylacetylene (Table 1, entries 18 and 19). alkyne was carried out using UV-vis spectroscopy, which suggested
With the optimized reaction conditions in hand, next we possible interaction between Ni(II) and propargyl alcohol and that
explored the substrate scope by varying the arylalkyne 1 as well of Ag(I) with phenyl acetylene (ESI†). The above result encouraged
as the -ynolic substrate 2 (Table 2). With stepwise substitution us to further investigate the interactions using 1H NMR as a probe
of the hydrogen atoms at the C-1 position (methylene group in CDCl3 or DMSO-d6 as a solvent with 2-methylbut-3-yn-2-ol 2c
next to –OH) of propargyl alcohol with a methyl group, the and phenylacetylene 1a as the representative reagents and
reaction time increases (Table 2, products 3b, 3c, 3f, 3g, 3j, 3k, 1,2,3-trimethoxybenzene (TMB) as the internal reference (ESI†).
3n, 3o, 3r and 3s). A similar trend has been noted with Upon incremental addition of Ni(II), the intensity of the –OH
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Table 2 Substrate scope for the hetero cross coupling of different
alkynes with Ni(OAc)2Á4H2O and AgOTfa
Fig. 1 Proposed mechanism for the formation of 1,3-hetero coupled
diynes.
silver acetylide.17 Based on the above results, a plausible
mechanism is proposed (Fig. 1, L = OAc or donor ligand). The
mechanism invokes prior activation of propargyl alcohol by
Ni(II) to generate I, and the formation of silver(I)acetylide II
from phenyl acetylene and Ag(I). A transmetallation reaction
involving I and II would generate the nickel(II) acetylide inter-
mediate III. As the propargylic (sp)C–H in III is activated by the
nickel centre, we suggest a metallation step by the silver salt to
give intermediate IV and sequential transmetallation to yield
the crucial intermediate V. A reductive elimination from V
would generate the desired hetero-coupled diyne product along
with Ni(0). The latter is expected to oxidize by air to generate
Ni(II), thereby completing the catalytic cycle.18
In conclusion, we report an inexpensive, milder, aerobic
method for the synthesis of unsymmetrical conjugated diynes from
functionally different alkynes by oxidative cross-coupling. This has
been successfully achieved by simply mixing two different transition
metals salts Ni(OAc)2Á4H2O and AgOTf in catalytic amounts. This
method is more efficient and atom economic. It shows a good
functional group tolerance and substrate scope with good to
excellent yields of the desired product. The formation of hetero
coupled diynes instead of homocoupled analogues has brought
high selectivity without any base, ligand and additives. In addition,
it is the first example of a Ni(II)/Ag(I) cooperative system which
promotes efficient hetero-coupling of two different alkynes. We
believe that the bimetallic system could potentially open up newer
C–H activation strategies involving sp(C) and sp2(C) centres. Work
in this direction including mechanistic studies is in progress.
AM thanks UGC for a fellowship.
a
Reaction conditions: arylalkyne 1 (0.25 mmol), alkyne 2 (0.5 mmol),
[Ag] (10 mol%), [Ni] (10 mol%), solvent (1 ml), 110 1C, air.
peak of propargyl alcohol 2c slowly decreased without causing
any significant change in other peaks, which suggests the
binding of propargyl alcohol to Ni(II). On the other hand,
marginal peak shifts were noticed when 2c and Ag(I) were
mixed.17 In sharp contrast, upon mixing phenyl acetylene 1a
and AgOTf in CDCl3, a white precipitate was instantly obtained.
The precipitate was dissolved in DMSO-d6 and 1H NMR was
recorded. In the resulting spectrum, the –CH peak of phenyl
acetylene 1a was completely absent and the aromatic region
Conflicts of interest
was shifted, suggesting the formation of the corresponding There are no conflicts to declare.
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